Chemistry

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4 papers in the last four weeks, against 2 the four weeks before. 0.0% of all new papers.

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Latest papers 29

Oct 1, 2026cs.LG

Higher-Order Molecular Grammars for Generative and Foundation Models in Chemistry

Molecular learning models are strongly shaped by their underlying representations. Yet standard sequential and graph formalisms struggle to explicitly encode higher-order topology, such as ring systems and recurring motifs. Existing higher-order representations can capture these structures directly, but they are often computationally demanding and difficult to decode into valid molecules. Here, we introduce Higher-order Grammar Representation (HGR), a principled, topology-aware framework that lifts molecules to combinatorial complexes and parses each complex into a compact sequence of production rules under a context-free higher-order grammar. By serialising higher-order topology into rule sequences, HGR makes these structures directly compatible with standard sequence models, avoiding the computational overhead of explicit higher-order encodings while preserving topological expressiveness. To reduce benchmark bias towards simple ring systems, we construct RingDiv, a ring-enriched benchmark containing 1.18 million molecules, including the curated RingDiv300k subset, and introduce the ring diversity index (RDI) to quantify ring-system coverage. In molecular generation, HGR-based models uniquely combine 100% validity by construction with leading distributional alignment, ranking first in FCD on all five generation benchmarks. In representation learning, HGR-FM achieves the highest mean AUC across seven MoleculeNet benchmarks under both transfer protocols, improving on the strongest baseline by 8.3 and 3.3 AUC points under probing and full fine-tuning, respectively. Collectively, these results establish HGR as an efficient higher-order representation for molecular generation and transferable representation learning.

Yiming Huang, Yujie Zeng, Vijay Prakash Dwivedi +4

Department of Computing, Imperial College London, London, UK · School of Electronic Engineering and Computer Science, Queen Mary University of London, London, UK · Department of Computer Science, Stanford University, Stanford, CA, USA +1

Molecular Generation Moleculenet Chemistry Context-Free Grammars Foundation Model

Oct 1, 2026cs.LG

Latent JEPA: Abstract Future Prediction for Latent Reasoning in Chemistry

Large language models offer a promising foundation for chemical reasoning, bringing together chemical knowledge and multistep problem solving. Chemical intuition can provide an initial sense of plausible outcomes before the details of a solution are fully worked out. Inspired by how such expectations complement explicit analysis, we study how continuous latent thoughts can be trained to anticipate informative aspects of future solutions without verbalizing every intermediate step. We introduce Latent JEPA, a framework that combines autoregressive learning with joint-embedding prediction of one or more future views. For chemical reasoning, we develop textual and molecular prediction objectives that connect latent thoughts to both subsequent reasoning and molecular outcomes. Experiments on ChemCoTBench show gains in molecular optimization and on several editing and reaction metrics. Representation analyses show that future prediction makes latent thoughts more informative about molecular outcomes and strengthens their correspondence with chemical structure. These findings support abstract future prediction as a learning principle for connecting continuous latent reasoning with scientific outcomes.

Xinjian Zhao, Yaoyao Xu, Xuemin Chen +2

School of Data Science, The Chinese University of Hong Kong, Shenzhen · Shanghai Artificial Intelligence Laboratory

Chemistry Efficient Latent Reasoning Latent Prediction Molecular Property Prediction Video Joint Embedding Predictive Architecture Performance Metric

Sep 28, 2026cs.LG

Drug-Target Interaction Prediction via Hierarchical Sequential Cross-Attention over Chemical and Protein Language Models

Predicting Drug-Target Interactions~(DTIs) is a central task in computational drug discovery, with direct applications in virtual screening, drug repurposing, and therapeutic candidate prioritization. Although recent deep learning methods have improved DTI prediction, many sequence-based models still process drugs and proteins independently and only combine their representations at a late prediction stage. This limits their ability to explicitly model cross-molecular dependencies between chemical substructures and protein sequence regions. In this paper, we propose a sequence-only DTI prediction architecture that combines two pre-trained language models, ChemBERTa for drug SMILES strings and ESM-2 for protein amino acid sequences, with a hierarchical interaction module. The proposed model first extracts contextual representations using pre-trained encoders, then applies 1D convolutional layers to condense local sequence patterns, followed by a sequential bidirectional cross-attention mechanism inspired by the induced-fit view of molecular recognition. Finally, attention-based pooling constructs fixed-size interaction-aware vectors for binary prediction. Experiments on BIOSNAP, Davis, and BindingDB show that the proposed model achieves the best performance on BIOSNAP, matches the best AUROC on Davis, and remains competitive on BindingDB while using only 25.2 million trainable parameters. Ablation results confirm the contribution of both the CNN and cross-attention modules, and cold-start experiments indicate promising generalization to unseen proteins and drugs.

Khadidja Henni, Hamza Abdelali, Abdelkrim Aries +4

I2A institute, T´ELUQ University, Montreal, QC, Canada · LIO, CRCHUM, Montreal, QC, Canada · LCSI, ESI, Algiers, Algeria +3

Protein Cross-Attention Chemistry Language Modeling

Sep 27, 2026cs.LG

ChemOPD: Multi-Teacher On-Policy Distillation for Multi-Task Chemical Reasoning

Large language models are increasingly expected to support diverse chemical reasoning capabilities within a unified model. One approach is to develop specialized capabilities separately and consolidate them through multi-teacher on-policy distillation, but this raises two questions: how should specialization be organized, and how should specialist guidance be integrated? We introduce ChemOPD, which addresses both. We estimate task affinities from supervised fine-tuning gradients and solve a constrained mixed-integer program(MIP) to construct partially overlapping specialist groups. During distillation, we retain a generalist teacher trained on all tasks so that specialist guidance supplements rather than replaces its supervision. Our anchor-residual objective gradually increases the routed specialist's contribution on student-generated responses. On ChemCoTBench, affinity-guided specialization produces task-dependent gains over the generalist teacher and improves several capabilities beyond semantic task grouping. Yet stronger teacher-side performance does not automatically yield stronger students: with the same specialists and routes, anchor-residual OPD improves most reported metrics over specialist-only distillation and realizes a larger share of the available teacher gains. These results highlight specialization and capability integration as connected but distinct design problems in chemical reasoning.

Yaoyao Xu, Xinjian Zhao, Xiaozhuang Song +2

School of Data Science, The Chinese University of Hong Kong, Shenzhen · Shanghai Artificial Intelligence Laboratory

Efficient On-Policy Distillation Chemical Structures Chemistry

Aug 31, 2026astro-ph.EP

Accelerating Chemical Kinetics for Exoplanet Atmospheres using Neural Networks

Observations increasingly reveal the coupled radiative, chemical, and dynamical processes that shape exoplanet atmospheres. Interpreting these atmospheres requires models that can capture this complexity. However, multidimensional models remain fundamentally limited by computational cost, and answering key questions requires simulating the governing physical mechanisms at speeds classical methods cannot achieve. As a result, models often rely on simplifying approximations, such as equilibrium chemistry, even when those assumptions miss important effects. There is a pressing need for fast and accurate chemical kinetics solvers to model planetary atmospheres. Here we present a machine learning local-box chemical kinetics solver for exoplanet atmospheres using a residual flow-map architecture. We demonstrate that this surrogate model is several orders of magnitude faster than a classical solver, achieving microsecond-scale inference while retaining percent-level accuracy. The surrogate model covers a parameter space that spans

T=300

-

3000

K,

P=10^{-6}

-

10^{4}

bar,

Δt=10^{-3}

-

10^{8}

s, and compositions ranging from

10^{-2}

to

10^{3}

times solar in both C/O ratio and metallicity. Our model outperforms several commonly used machine learning architectures and performs robustly under the extreme stiffness characteristic of atmospheric chemistry. The machine learning framework presented here is a flexible and efficient approach to emulating state-to-state flow-map problems that commonly arise in numerical simulations.

Isaac Malsky, Xi Zhang, Tiffany Kataria +5

Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109, USA · Department of Earth and Planetary Sciences, University of California Santa Cruz, Santa Cruz, CA 95064, USA · Division of Physics, Mathematics and Astronomy, California Institute of Technology, Pasadena, CA 91125, USA +4

Exoplanet Atmospheres Kinetics Atmospheric Dynamics Surrogate Models Chemistry Solvers+1

Aug 31, 2026cs.LG

One Policy Is Enough: Single-Agent Reinforcement Learning Outperforms Tree Search for Chemistry Tool Learning

Chemistry questions often demand exact computation and database lookups that a language model cannot supply from its parameters, so it must reach for external tools. Tool use here is a three-part problem: select the right tool from a large pool, fill it with correctly typed arguments, and chain calls so that each consumes the outputs of the last. CheMatAgent, a previously published system, addresses this with hierarchical evolutionary MCTS: separate policy and execution models searching tool-call trees under two learned critics, one regressed partly onto GPT-assigned scores. We show that a single policy suffices. Our model interleaves reasoning, tool calls, and returns in one left-to-right generation, trained by a supervised warm-up and then outcome-level reinforcement learning against a programmatic reward read directly off the gold call chain, which leaves no learned critic and no judge in the training loop. On ChemToolBench multiple-tool comprehensive chemistry, on both backbones CheMatAgent use, we improve Tool F1 by 5.5% and Return F1 by 9.6% on Qwen-2.5-7B, and by 3.7% and 3.9% on Llama-3.1-8B, compared with their strongest search configuration, at one model invocation per question, against a search whose cost grows with the tree; we also lead answer Pass Rate on Qwen-2.5-7B.

Armin Dariani, Sifan Wu, Bang Liu +1

1DIRO, Université de Montréal · 2Mila - Quebec Artificial Intelligence Institute · 3Innovation Campus Delaware, Air Liquide

Chemistry Monte Carlo Tree Search Offline Reinforcement Learning Trees

Aug 31, 2026cs.LG

CoMPASS: Collaborative Molecular Property Prediction via Adaptive Small-Large Model Synergy

Accurate molecular property prediction requires both statistical reliability and chemical reasoning. Graph neural networks can be calibrated directly on labeled assays but remain limited by the coverage of their training data. Large language models (LLMs) can compare molecular evidence and articulate chemical rationales, yet are unreliable as standalone quantitative predictors. The central challenge is therefore to determine when an LLM should influence a calibrated model and by how much. Here we present CoMPASS, a retrieval-calibrated framework for small-large model collaboration. CoMPASS retains a graph attention network (GAT) as the predictive anchor, retrieves locally relevant training molecules, provides attention-grounded evidence to an LLM, and converts its proposal into a bounded correction through an agreement-aware gate. Across six classification and two regression benchmarks, CoMPASS improves the GAT anchor in regions of correctable uncertainty while limiting LLM intervention in high-confidence regimes. Ablations show that the gains arise from validation-calibrated retrieval and bounded fusion rather than prompting alone. These results suggest that generative reasoning should augment calibrated prediction through evidence-grounded, controlled corrections rather than direct output replacement. Code is available at https://github.com/littlepeachs/CoMPASS.

Wentao Li, Jiangjie Qiu, Yijun Li +2

Beijing Key Laboratory of Artificial Intelligence for Advanced Chemical Engineering Materials · State Key Laboratory of Chemical Engineering and Low-Carbon Technology · Department of Chemical Engineering, Tsinghua University

Molecular Property Prediction Chemistry Small Reasoning Model

Aug 4, 2026cs.CV

MinerU.Chem: A High-Precision System for Optical Chemical Structure and Reaction Recognition

In organic chemistry papers and patents, molecular structures, reaction schemes, and experimental conditions are often presented as molecular structure depictions, reaction diagrams, and complex tables or figures. Such information is difficult for general-purpose document parsing systems to directly convert into machine-readable data. This limits data production for organic chemistry knowledge base construction and for AI for Chemistry tasks such as reaction prediction, retrosynthesis, condition recommendation, molecular property prediction, and drug molecule design. This report introduces MinerU-Chem, a document parsing system for organic chemistry literature integrated into the MinerU online platform. Built on top of MinerU's general document parsing pipeline, MinerU-Chem adds five chemistry-specific modules: chemistry relevance filtering, molecular structure detection, molecule identifier extraction, molecular structure recognition, and reaction scheme parsing. Together, these modules convert organic-chemistry-related image regions in documents into a Molecule Summary List and a Reaction Summary List. For molecular structure recognition, MinerU-Chem uses CARBON (Complex Atomic Representation and Bonding Object Notation) as its core representation. CARBON enables recognition results to preserve both the visual layout of the original image and complex chemical semantics, while supporting the export of standard downstream formats such as MolFile and SMILES. On the SMILES-evaluable subset of MolRecBench-Wild (N=2,392), MinerU-Chem's molecular structure recognition module achieves a SMILES exact-match accuracy of 93.02%, outperforming the best evaluated comparison system, GPT-5.6-Sol (74.87%), by 18.15 percentage points. The system has been integrated into the MinerU online platform and is available at https://mineru.net/OpenSourceTools/Extractor .

Haote Yang, Jiang Wu, Jingchao Wang +42

Chemical Structures Chemistry Molecules Reaction Precision

Aug 3, 2026cs.LG

onepot-Bench 0: towards lab-aware in silico chemistry benchmarks

Language models are playing an increasingly important role in laboratory science, performing tasks such as experiment planning, execution, and post-hoc analysis. However, precisely measuring their abilities is difficult, as scientific capabilities require a mixture of both problem-solving skills and domain-specific intuition. Existing evaluations rarely measure the capabilities required to make reliable decisions in a physical laboratory and often rely on public data that may have appeared in model training corpora. We introduce onepot-Bench 0, a proprietary benchmark suite for evaluating language models on synthetic chemistry capabilities relevant to wet-lab execution. onepot-Bench 0 comprises three complementary evaluations: ChemAbacus measures tool-free cheminformatics literacy and numerical reasoning; SynthRefusal characterizes safety and refusal behavior across a variety of benign, controlled, and designer-drug targets; and SynthBench evaluates reaction-outcome prediction and catalyst selection using private experimental data generated in our laboratory. Together, these evaluations probe basic competency, reliability, and deeper knowledge, all skills which are required for reliable performance in the lab.

Brandon Wang, Andrei S. Tyrin, Daniil A. Boiko

Onepot AI, Inc.

Jul 30, 2026cs.CL

AskChem: Claim-Centered Infrastructure for Chemistry Literature Synthesis

Chemistry literature synthesis often requires assembling specific findings scattered across many publications, yet existing literature-search systems primarily return ranked document lists. As a result, scientists and AI agents need to locate relevant information, verify their provenance, and assemble cross-paper answers manually. We present AskChem, a claim-centered infrastructure for cross-paper chemistry search. AskChem changes the unit of retrieval from the paper to the provenance-carrying claim: each paper is converted into atomic, typed claims, each grounded by a source DOI and a verbatim quote or an explicit evidence locator. Over this shared claim store, AskChem exposes complementary structures for search and synthesis: a stabilized faceted taxonomy for hierarchical retrieval and browsing, an evidence graph linking claims through relations, and an exploratory living taxonomy that situates indexed papers under scientific principles. AskChem currently indexes 2.4M claims from 147K papers and provides a web interface, as well as REST, SDK, and MCP access for AI agents. On AskChem-Bench, grounding a GPT-5.5 reader in AskChem yields 100% resolvable DOIs, compared with 88.3% without retrieval, and the highest citation density among five tested systems. AskChem is live at https://askchem.org.

Bing Yan, Gregory Wolfe, Stefano Martiniani +1

New York University · Matterstack, Inc.

Chemistry Scholar Information Database Citations Synthesis Infrastructure

Jul 30, 2026q-bio.PE

Hash Chemistry: Minimal Models for Evolutionary Growth of Complexity

Hash Chemistry is a family of minimalistic evolutionary models in which a deterministic hash function assigns a scalar score to entities of arbitrary size, opening a combinatorially vast possibility space (a ``cardinality leap''). Since its introduction, the idea has been realized in several settings, from the original spatial formulation to a fast non-spatial variant and then to structural cellular models. Here we review the Hash Chemistry family as a coherent modeling framework and use it to explore how minimal systems can demonstrate the mechanisms behind multiscale open-ended evolutionary dynamics. The most recent model, Structural Cellular Hash Chemistry (SCHC), successfully demonstrated multiscale ecological interaction/adaptation and complexity growth of replicators in a computationally efficient manner. In this study, we first extend SCHC to incorporate spatial locality and dyadicity of competitive interactions among replicating structures. We show this extension substantially enhances SCHC's evolutionary dynamics. Furthermore, we explore SCHC in a significantly larger spatial domain using a GPU-accelerated implementation. We show that the size of the space acts as a control parameter for a stochastic, nucleation-like transition between a compact-replicator regime and a runaway size-dominance regime, and we separate the responsible mechanism into a non-spatial, size-biased sampling feedback and a finite-size spatial effect. Altogether, these results illustrate the rich potential of Hash Chemistry as a minimal, mechanistically transparent testbed for studying open-ended evolution across scales.

Ilya Horiguchi, Hiroki Sayama

Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo, 153-8902, Japan. · Binghamton Center of Complex Systems, Binghamton University, State University of New York, Binghamton, NY, 13902, USA. · Systems Engineering, Cornell University, Ithaca, NY, 14850, USA. +1

Evolutionary Optimization Methods Locality-Sensitive Hashing Chemistry Cardinality Multiscale Less Data

Jul 21, 2026cs.DM

Towards chemistries in dynamical systems

Chemistry describes aspects of the universe in terms of molecules and their reactions. In this exploratory work we present a way to describe aspects of any dynamical system in similar terms. To describe a dynamical system in this way three decisions have to be made. The first is how many different "places" there are at which molecules or chemical species can occur; the second is how to determine the species present (or not) at each place; and the third is the set of transitions and reactions that can occur between the species in the various places. For these choices to be compatible with the state update of the dynamical system each state must be able to determine transitions that take the currently occurring molecules to those occurring in the updated state. We also propose an additional requirement that there is always a unique way to choose the least amount of transitions occurring during state updates. We discuss gliders in the game of life cellular and argue that when following their definition of according to Randall Beer they satisfy the additional criterion as well. We also point out some issues with the approach.

Martin Biehl, Nathaniel Virgo

Cross Labs, Cross Compass, Japan · University of Hertfordshire, United Kingdom

Dynamical Systems Reaction Transitions Chemical Structures Chemistry

Jul 19, 2026cs.LG

Grounded verification of chemical and materials reasoning: detection is the bottleneck

Large language models confabulate chemical objects (molecular formulas, space groups, formation energies) in fluent reasoning traces, concentrated on long-tail entities where confidence is least trustworthy. Deterministic, database-grounded verification can catch and repair such errors without the coverage cost of blanket retrieval; the binding constraint, we find, is detection, not repair. Our tiered verifier extracts each checkable claim, checks it against authoritative databases and physics, and feeds the reference into a gated correction loop. Across four models and 528 condition-pinned prompts, gated correction cuts committed-formula error from 22% to 4% at

3.2\times

fewer retrievals than blanket augmentation, beating a conversational oracle. Repair succeeds wherever a flag fires (80--97%); the bottleneck is in-loop detection recall. Grounding improves the final answer only when the verifier's scope reaches the deliverable (83% to 90%), and the lift appears only where extractable long-tail error exists: absent on near-ceiling physical constants, large on isotope half-lives (11% to 0%).

Can Polat, Mustafa Kurban, Erchin Serpedin +1

Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, USA · Department of Electrical and Computer Engineering, Texas A&M University at Qatar, Doha, Qatar · Department of Prosthetics and Orthotics, Ankara University, Ankara, Turkey +1

Chemistry Confabulation Materials Bottlenecks Extraction

Jul 14, 2026cs.LG

Learning Mechanistic Reasoning for Chemical Reactions with Large Language Models

Reaction mechanisms consist of the step-by-step sequences of elementary reactions that explain chemical transformations. Learning the mechanism logic is therefore essential for enhancing the fundamental chemical intelligence of large language models (LLMs). The stepwise deduction of reaction mechanism aligns naturally with the reasoning paradigms of reasoning LLMs. However, current chemical LLMs primarily emphasize coarse-grained name reactions for product prediction and retrosynthesis, often leading to physical inconsistencies and hallucinations. In contrast, specialized small-scale generative models for mechanism inference typically suffer from restricted generalization capacity across diverse chemical spaces. To overcome these limitations, we built a novel, large-scale reasoning dataset of reaction mechanisms. Furthermore, we established the FukuyamaBench, a difficult benchmark derived from Fukuyama's Advanced Organic Reaction Mechanism book, to rigorously evaluate model performance on hierarchical mechanism reasoning. Our fine-tuned Qwen3-30B-A3B achieves 8.3% exact pathway match on FukuyamaBench Set~A, surpassing the specialized FlowER model (5.1%), demonstrating that mechanism-aware training substantially enhances chemical reasoning in language models.

Xingyu Dang, Haocheng Tang, Junmei Wang +1

Department of Computer Science, Princeton University, Princeton, NJ, 08540, United States · School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, 15261, United States · Khoury College of Computer Science, Northeastern University, Boston, MA, 02115, United States +2

Reaction Chemistry LLM Reasoning Strategies

Jul 6, 2026cs.LG

URSA: Chemistry-Aware Benchmark for Utilitarian Retrosynthesis Assessment

Synthesis planning aiming to find pathways of reactions for a target molecule is one of the most important and challenging tasks in drug discovery. Recent progress has produced both specialized deep-learning retrosynthesis systems and general-purpose large language models, but objective comparison remains difficult due to the lack of flexible, chemically interpretable benchmarking protocols. In the current study, we are introducing the URSA (Utilitarian RetroSynthesis Assessment) evaluation framework that provides the opportunity to benchmark the synthetic routes not only from a formal perspective, such as convergence to commercially available starting materials, but also from a chemical plausibility perspective, mimicking the way expert chemists evaluate the reactions and routes. The study covers a comprehensive evaluation of both conventional end-to-end retrosynthesis solutions and LLMs for the synthesis planning task on a set of novel, diverse target molecules with undisclosed synthetic routes, which represent realistic tasks in the daily drug design routine. We find that while LLMs can support high-level strategic planning, they currently underperform specialized retrosynthesis models in reliably solving synthesis planning tasks.

Bogdan Zagribelnyy, Ivan Ilin, Nikita Bondarev +7

Insilico Medicine AI Limited, Masdar City, Abu Dhabi, UAE · Independent researcher · Insilico Medicine Canada Inc., Montreal, Quebec, Canada +1

Chemistry Drug Discovery Synthesis Physical Plausibility

Jul 2, 2026stat.ML

An Additive MLP-GNN Framework for Characterizing Chemical and Structural Contributions to Aqueous Solubility

Aqueous solubility is a key property in early-stage drug discovery, but most predictive models merge physicochemical descriptors and molecular graph information into a single representation, obscuring whether a prediction is driven by global chemistry, molecular structure, or both. We present an additive deep-learning framework that keeps these two sources of information separate throughout training: physicochemical descriptors are encoded by a multilayer perceptron (the chemical branch) and molecular graph topology by a graph neural network (the structural branch), with the two outputs combined only at the prediction stage through an additive model with an optional multiplicative interaction. This design provides a direct decomposition of chemical and structural components that can be examined separately after training. Furthermore, pretraining on the larger AqSolDB dataset and fine-tuning on the smaller BigSolDB2 dataset substantially improve accuracy and reduce run-to-run variations, indicating generalizability of the learned features from the data-rich settings. We further interpret the fitted model using best linear projections of the branch outputs, molecule-level embedding summaries across solubility classes, and atom-level GNNExplainer masks aggregated over functional groups. These analyses show that the chemical branch aligns with familiar physicochemical descriptors, while the structural branch captures graph-topological and functional-group patterns associated with solubility. Across both datasets, the framework attains competitive predictive performance while making the distinct roles of chemical and structural information more transparent.

Sampreeti Bhattacharya, Arkaprava Roy

Transferable Implicit Solvent Machine Learning Potential Molecular Property Prediction Chemistry Drug Discovery Gnn-Based Detectors Deep Learning Framework

Jun 22, 2026cs.LG

Rethinking Molecular Graph Backdoors under Chemistry-aware Admission

Backdoor attacks on molecular graph neural networks (GNNs) are typically evaluated as abstract graph edits, but real molecular learning pipelines do not train on arbitrary graphs. Molecular records must first survive parsing, sanitization, canonicalization, and graph-string consistency checks. We formalize this overlooked admission stage as ChemGuard, an operational protocol for testing whether a submitted molecular record can enter a realistic learning pipeline, while complementing existing defenses. ChemGuard admits a record only when its molecular string is sanitizable and the graph reconstructed from that string matches the submitted molecular graph. Under this operational view, many existing graph-based backdoors lose much of their apparent efficacy because their poisons are chemically invalid or representation-inconsistent. We then show that admission checks alone are insufficient to rule out molecular backdoors. We propose ChemBack, an admission-aware molecular backdoor attack that constructs chemically feasible motif-anchor attachments and ranks admitted candidates by fingerprint-based Tanimoto similarity to clean target-class molecules. ChemBack is model-free during trigger selection, using molecular structures, target labels, fingerprints, and public validity checks, but no victim model, surrogate GNN, learned embedding, gradient, logit, or training-code access. Across molecular benchmarks, validators, architectures, and defenses, \textbf{ChemBack} achieves high attack success with fully admitted poisons while preserving clean accuracy. Our results reveal a two-sided lesson, chemistry-aware admission suppresses many graph-only backdoors, yet chemically valid and target-aligned molecular backdoors remain a practical threat.

Thinh T. H. Nguyen, Sze Jue Yang, Khoa D. Doan +2

VinUniversity, Hanoi, Vietnam · Universiti Malaya

Chemistry Graph Neural Networks

Jun 4, 2026cs.LG

MolE-RAG: Molecular Structure-Enhanced Retrieval-Augmented Generation for Chemistry

Large language models (LLMs) have shown promise for molecular property prediction, but their ability to reason over chemical structures remains limited, as molecular representations such as SMILES differ substantially from the natural language on which LLMs are primarily trained. To bridge this semantic and chemical knowledge gap, we propose MolE-RAG, a training-free, molecule-centric retrieval-augmented generation framework for LLM-based molecular property prediction. MolE-RAG augments each prediction with three complementary sources of inference-time context: retrieved chemistry literature, molecule-specific information including compound synonyms, identifiers, functional group annotations, and physicochemical descriptors, and structurally similar molecules retrieved from the training set. We evaluate MolE-RAG across nine molecular property prediction tasks using proprietary, chemistry-specialized, and open-source LLMs. Across general-purpose LLMs, MolE-RAG improves ROC-AUC by up to 28 percentage points on classification tasks and reduces regression RMSE by up to 67% relative to a SMILES-only baseline. We further find that the utility of each context source varies across models and tasks, with different models benefiting most from textual retrieval, molecular context, or structural retrieval. These results suggest that molecule-centric retrieval can improve LLM-based molecular property prediction without model fine-tuning while providing a flexible framework for integrating heterogeneous chemical knowledge at inference time.

Joey Chan, Wonbin Kweon, Ashley Shin +4

University of Illinois Urbana-Champaign · University of California, San Diego

Molecular Property Prediction Chemical Structures Chemistry Hievi-Rag

Jun 2, 2026cs.AI

From Answers to States: Verifiable Process-Level Evaluation of Chemical Reasoning in Large Language Models

Large language models are increasingly used as chemistry assistants, yet most chemistry benchmarks still score only final answers. This masks a critical failure mode: a model may output the correct molecule, product, or option while its reasoning violates chemical logic. Existing process-level evaluators are hard to scale because LLM judges and human step-level process annotation are costly, inconsistent, and vulnerable to hallucination. We introduce ChemCoTBench-V2, a rule-verifiable diagnostic benchmark for low-cost, auditable evaluation of structured, verifier-addressable chemical reasoning traces. It spans molecular understanding, molecule editing, molecular optimization, and reaction prediction, with 5,620 evaluation samples across 18 reporting tasks. Models must expose key intermediate steps in expert-designed templates, and those steps are checked with deterministic chemistry rules and, for closed-answer tasks, reference traces rather than another LLM judge. Open-ended molecular optimization is evaluated with oracle-verifiable state constraints rather than strict trace matching. The benchmark reports three separate signals: final-answer correctness, template adherence, and step-wise verifier correctness over expert-refined intermediate commitments. Experiments on frontier models reveal a persistent gap between final-answer success and structured-reasoning-state consistency: models often follow the requested format while failing chemical-step checks, or answer correctly with weak supporting reasoning. ChemCoTBench-V2 enables fine-grained model comparison and identifies the concrete step at which the trace first violates the verifier.

Hongyu Guo, Hao Li, He Cao +2

Peking University, Shenzhen Graduate School · International Digital Economy Academy (IDEA)

Chemistry Answer

May 27, 2026cs.LG

AtomComposer: Discovering Chemical Space from First Principles with Reinforcement Learning

Discovering novel stable molecules without training data remains a grand scientific challenge. Current molecular generative models are trained on large, pre-curated datasets, which introduce biases and limit exploration of novel chemistry. In contrast, we propose a new paradigm: autonomous, generalized agents capable of mapping vast, unknown chemical spaces without any pretraining. For the first time, we present AtomComposer, a self-guided agent that autonomously constructs valid 3D isomers under stoichiometric constraints and is trained exclusively online using reinforcement learning. Unlike existing approaches that generally overfit to a specific chemical formula, we establish a multi-composition training scheme that enables a broad generalization across diverse chemistry, guided by energy- and validity-based rewards. Our agent can discover up to an order of magnitude more valid isomers on unseen test formulas than existing single-composition reinforcement-learning baselines trained with per-step energy rewards. These results fulfill the promise of online reinforcement learning as a powerful paradigm for scalable, from-scratch exploration of chemical configuration space.

Bjarke Hastrup, Francois Cornet, Tejs Vegge +1

Dept. of Energy Conversion and Storage, Technical University of Denmark, Denmark · Dept. of Applied Mathematics and Computer Science, Technical University of Denmark, Denmark · Pioneer Center for Accelerating P2X Materials Discovery (CAPeX), Kgs. Lyngby, Denmark

Chemical Structures Chemistry Generative Models

May 21, 2026astro-ph.IM

Spectra as Language: Large Language Models for Scalable Stellar Parameter and Abundance Inference

Stellar spectra encode key information on the physical properties and chemical compositions of stars. Accurate stellar parameter determination is essential for addressing major questions such as galaxy and stellar evolution. Large-scale spectroscopic surveys have accumulated unprecedented spectral data. Traditional feature extraction or model-fitting approaches struggle with high-dimensional, massive datasets, limited generalization, and computational inefficiency. Recent advances in large language models demonstrate strong generalization and feature-learning in tasks like natural language processing, DNA/RNA sequence analysis, and protein/chemical parsing. Stellar spectra are continuous sequential signals, enabling the transfer of language models to stellar spectroscopy. Here, we propose a two-stage large language model framework for stellar parameter inference, achieving accurate estimation of effective temperature, surface gravity, metallicity, and abundances of ~20 chemical elements. Scaling-law analyses show systematic performance improvements with increasing data, providing a scalable framework for forthcoming large-scale surveys.

Hai-Ling Lu, Yu-Yang Li, Yin-Bi Li +4

National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100101, China · University of Chinese Academy of Sciences, Beijing 100049, China · School of Astronomy and Space Science, University of Chinese Academy of Sciences, Beijing 100049, China +1

Astronomical Images Chemistry

May 13, 2026cs.LG

Reducing cross-sample prediction churn in scientific machine learning

Scientific machine learning reports predictive performance. It does not report whether the same prediction would survive a different draw of training data. Across

9

chemistry benchmarks, two classifiers trained on independent bootstraps of the same training set agree on aggregate accuracy to within

1.3\text{--}4.2

percentage points but disagree on the class label of

8.0\text{--}21.8\%

of test molecules. We call this gap \emph{cross-sample prediction churn}. The standard parameter-side techniques (deep ensembles, MC dropout, stochastic weight averaging) do not reduce this gap; two data-side methods do. The first is

K

-bootstrap bagging, which cuts the rate

40\text{--}54\%

on every dataset at no accuracy cost (

K{\times}

-ERM compute). The second is \emph{twin-bootstrap}, our proposal: two networks trained jointly on independent bootstraps with a sym-KL consistency loss between their predictions, which at matched

2{\times}

-ERM compute reduces churn a further median

45\%

beyond bagging-

K{=}2

. Cross-sample prediction churn deserves a column alongside predictive performance in scientific-ML benchmark reports, because without it the parameter-side and data-side methods are indistinguishable on the metric they actually differ on.

Gordan Prastalo, Kevin Maik Jablonka

Helmholtz-Zentrum Berlin für Materialien und Energie GmbH, Hahn-Meitner-Platz 1, 14109 Berlin, Germany · HIPOLE Jena (Helmholtz Institute for Polymers in Energy Applications Jena), Lessingstrasse 12–14, 077432026 Jena, Germany · Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743 Jena, Germany +2

Churn Prediction Model-Based Bootstrap Clinical Prediction Mle-Bench Lite Chemistry

May 7, 2026cs.LG

SMolLM: Small Language Models Learn Small Molecular Grammar

Language models for molecular design have scaled to hundreds of millions of parameters, yet how they learn chemical grammar is poorly understood. We train SMolLM, a 53K-parameter weight-shared transformer, to generate novel SMILES with 95% validity on the ZINC-250K drug-like-molecule benchmark, outperforming a standard GPT with 10 times more parameters. Mechanistically, the same block resolves SMILES constraints across passes in a fixed hierarchy: brackets first, rings second, and valence last, as shown by error classification and linear probing, with ablation isolating the bracket-matching head. Together, these results yield a compact, mechanistically interpretable molecular generator and a testbed for studying iterative computation in formal-language domains.

Akhil Jindal, Harang Ju

Moku

Molecular Generation Chemistry Context-Free Grammars

May 5, 2026cs.LG

Pretrained Model Representations as Acquisition Signals for Active Learning of MLIPs

Training machine learning interatomic potentials (MLIPs) for reactive chemistry is often bottlenecked by the high cost of quantum chemical labels and the scarcity of transition state configurations in candidate pools. Active learning (AL) can mitigate these costs, but its effectiveness hinges on the acquisition rule. We investigate whether the latent space of a pretrained MLIP already contains the information necessary for effective acquisition, eliminating the need for auxiliary uncertainty heads, Bayesian training and fine-tuning, or committee ensembles. We introduce two acquisition signals derived directly from a pretrained MACE potential: a finite-width neural tangent kernel (NTK) and an activation kernel built from hidden latent space features. On reactive-chemistry benchmarks, both kernels consistently outperform fixed-descriptor baselines, committee disagreement, and random acquisition, reducing the data required to reach performance targets by an average of 38% for energy error and 28% for force error. We further show that the pretrained model induces similarity spaces that preserve chemically meaningful structure and provide more reliable residual uncertainty estimates than randomly initialised or fixed-descriptor-based kernels. Our results suggest that pretraining aligns latent-space geometry with model error, yielding a practical and sufficient acquisition signal for reactive MLIP fine-tuning.

Eszter Varga-Umbrich, Shikha Surana, Paul Duckworth +3

1InstaDeep · University of Cambridge

Interatomic Potentials Active Learning Quantum Chemistry Pretraining Chemistry

May 4, 2026cs.CL

MolViBench: Evaluating LLMs on Molecular Vibe Coding

Molecular Vibe Coding, a paradigm where chemists interact with LLMs to generate executable programs for molecular tasks, has emerged as a flexible alternative to chemical agents with predefined tools, enabling chemists to express arbitrarily complex, customized workflows. Unlike general coding tasks, molecular coding imposes a distinctive challenge that LLMs should jointly equip programming, molecular understanding, and domain-specific reasoning capabilities. However, existing benchmarks remain disconnected. General code generation benchmarks such as HumanEval and SWE-bench require no chemistry knowledge, while chemistry-focused benchmarks such as S^2-Bench and ChemCoTBench evaluate knowledge recall or property prediction rather than executable code generation. To bridge this gap, we introduce MolViBench, the first benchmark tailored for Molecular Vibe Coding. MolViBench comprises 358 curated tasks across five cognitive levels, ranging from single-API recall to end-to-end virtual screening pipeline design, spanning 12 real-world drug discovery workflows. To rigorously assess generated code, we also propose a multi-layered evaluation framework that combines type-aware output comparison and AST-based API-semantic fallback analysis, which jointly measures executability and chemical correctness. We systematically evaluate 9 frontier coding LLMs and compare three real-world Molecular Vibe Coding paradigms, providing a practical and fine-grained testbed for diagnosing LLMs' coding capabilities in AI-accelerated molecular discovery.

Jiatong Li, Yuxuan Ren, Weida Wang +4

The Hong Kong Polytechnic University · National University of Singapore · Fudan University

Chemistry Vibe Coding Code Generation Large Language Model Benchmarks Screening

Apr 21, 2026cs.LG

When Active Learning Falls Short: An Empirical Study on Chemical Reaction Extraction

The rapid growth of chemical literature has generated vast amounts of unstructured data, where reaction information is particularly valuable for applications such as reaction predictions and drug design. However, the prohibitive cost of expert annotation has led to a scarcity of training data, severely hindering the performance of automatic reaction extraction. In this work, we conduct a systematic study of active learning for chemical reaction extraction. We integrate six uncertainty- and diversity-based strategies with pretrained transformer-CRF architectures, and evaluate them on product extraction and role labeling task. While several methods approach full-data performance with fewer labeled instances, learning curves are often non-monotonic and task-dependent. Our analysis shows that strong pretraining, structured CRF decoding, and label sparsity limit the stability of conventional active learning strategies. These findings provide practical insights for the effective use of active learning in chemical information extraction.

Simin Yu, Sufia Fathima

Data and Knowledge Engineering

Active Learning Chemistry Empirical Study

Aug 3, 2025cs.IR

ChEmbed: Enhancing Chemical Literature Search Through Domain-Specific Text Embeddings

Retrieval-Augmented Generation (RAG) systems in chemistry heavily depend on accurate and relevant retrieval of chemical literature. However, general-purpose text embedding models frequently fail to adequately represent complex chemical terminologies, resulting in suboptimal retrieval quality. Existing embedding models for chemistry are outdated, and none is tailored to chemical literature retrieval, leaving a substantial performance gap. To address this challenge, we introduce ChEmbed, the first purpose-built family of domain-adapted text embedding models engineered for chemical literature retrieval. These models are fine-tuned via contrastive learning on a dataset comprising chemistry-specific text from the PubChem, Semantic Scholar, and ChemRxiv corpora. To create effective training data, we employ large language models to synthetically generate queries, resulting in approximately 1.7 million high-quality query-passage pairs. Additionally, we augment the tokenizer by adding 900 chemically specialized tokens to previously unused slots, which reduces the fragmentation of chemical entities, such as IUPAC names. ChEmbed also maintains an 8192-token context length, enabling retrieval of longer passages than many open-source embedding models allow. Evaluated on our newly introduced ChemRxiv Retrieval benchmark, ChEmbed outperforms state-of-the-art general embedding models, raising MRR@10 from 0.781 to 0.882 (+10.1 pp). It also substantially outperforms domain-specific embedding models such as Chemical-BERT, improving MRR@10 from 0.096 to 0.882. A role-based retrieval analysis using PubChem descriptions and ChEBI annotations shows that the improvement extends to chemical-role queries. ChEmbed represents a practical, lightweight, and reproducible embedding solution that effectively improves chemical literature retrieval.

Ali Shiraee Kasmaee, Mohammad Khodadad, Mahdi Astaraki +4

Department of Computational Science and Engineering, McMaster University, Canada · BASF Canada Inc., Canada · BASF Corporation, USA

Chemistry Chemical Structures Text Embeddings Bert-Based Models Domain-Adapted Diffusion

Jun 13, 2025cs.IR

Chunk Twice, Embed Once: A Systematic Study of Segmentation and Representation Trade-offs in Chemistry-Aware Retrieval-Augmented Generation

The retrieval stage of retrieval-augmented generation (RAG) for scientific question answering depends on how documents are segmented and how chunks are represented in embedding space. This dependence is especially relevant to chemistry texts, which contain dense terminology, symbolic notation, quantitative evidence, and context associated with document structure. However, benchmark-based evidence on the interaction between chunking strategy and embedding model remains limited for chemistry-specific retrieval. Using ChemQuests, a corpus of 952 question-answer pairs from 151 ChemRxiv papers across 17 chemistry subfields, we construct chunk-level, Massive Text Embedding Benchmark (MTEB)-compatible retrieval benchmarks for controlled evaluation. We first screen 41 embedding models on the external chemistry retrieval benchmarks ChemNQRetrieval and ChemHotpotQARetrieval using a geometric-mean metric at rank 10 (Geom@10), which we validate against the full retrieval-metric profile. We then evaluate shortlisted models on ChemQuests-derived tasks across five chunking strategies, seven chunk sizes, and multiple overlap settings. Embedding choice is associated with the largest observed differences in evidence retrieval, with retrieval-tuned E5, Beijing Academy of Artificial Intelligence General Embedding (BGE), and Nomic models among the strongest overall. Within the evaluated grid, medium-to-large chunks combined with fixed-token, recursive-token, or hierarchical-section chunking provide a practical starting point for the retrieval stage of chemistry-aware RAG. Low overlap was generally favored where overlap variation was evaluated.

Mahmoud Amiri, Thomas Bocklitz

Leibniz Institute of Photonic Technology, Albert-Einstein-Strasse 9, 07745 Jena, Germany · Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, 07743 Jena, Germany

Chemistry Chunk Trade-Off

Date pendingphysics.chem-ph

El Agente Quntur: A research collaborator agent for quantum chemistry

Quantum chemistry is a foundational enabling tool for the fields of chemistry, materials science, computational biology and others. Despite of its power, the practical application of quantum chemistry simulations remains in the hands of qualified experts due to methodological complexity, software heterogeneity, and the need for informed interpretation of results. To bridge the accessibility gap for these tools and expand their reach to chemists with broader backgrounds, we introduce El Agente Quntur, a hierarchical, multi-agent AI system designed to operate not merely as an automation tool but as a research collaborator for computational quantum chemistry. Quntur was designed following three main strategies: i) elimination of hard-coded procedural policies in favour of reasoning-driven decisions, ii) construction of general and composable actions that facilitate generalization and efficiency, and iii) implementation of guided deep research to integrate abstract quantum-chemical reasoning across subdisciplines and a detailed understanding of the software's internal logic and syntax. Although instantiated in ORCA, these design principles are applicable to research agents more generally and easily expandable to additional quantum chemistry packages and beyond. Quntur supports the full range of calculations available in ORCA 6.0 and reasons over software documentation and scientific literature to plan, execute, adapt, and analyze in silico chemistry experiments following best practices. We discuss the advances and current bottlenecks in agentic systems operating at the research level in computational chemistry, and outline a roadmap toward a fully autonomous end-to-end computational chemistry research agent.

Juan B. Pérez-Sánchez, Yunheng Zou, Jorge A. Campos-Gonzalez-Angulo +12

Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON M5S 3H6, Canada · Vector Institute for Artificial Intelligence, W1140-108 College St., Schwartz Reisman Innovation Campus, Toronto, ON M5G 0C6, Canada · Acceleration Consortium, 700 University Ave., Toronto, ON M7A 2S4, Canada +6

Quantum Chemistry Chemistry